Mast cell activation test in the diagnosis of allergic disease and anaphylaxis

Abstract

BackgroundFood allergy is an increasing public health issue and the most common cause of life-threatening anaphylactic reactions. Conventional allergy tests assess for the presence of allergen-specific IgE, significantly overestimating the rate of true clinical allergy and resulting in overdiagnosis and adverse effect on health-related quality of life.ObjectiveTo undertake initial validation and assessment of a novel diagnostic tool, we used the mast cell activation test (MAT).MethodsPrimary human blood-derived mast cells (MCs) were generated from peripheral blood precursors, sensitized with patients' sera, and then incubated with allergen. MC degranulation was assessed by means of flow cytometry and mediator release. We compared the diagnostic performance of MATs with that of existing diagnostic tools to assess in a cohort of peanut-sensitized subjects undergoing double-blind, placebo-controlled challenge.ResultsHuman blood-derived MCs sensitized with sera from patients with peanut, grass pollen, and Hymenoptera (wasp venom) allergy demonstrated allergen-specific and dose-dependent degranulation, as determined based on both expression of surface activation markers (CD63 and CD107a) and functional assays (prostaglandin D2 and β-hexosaminidase release). In this cohort of peanut-sensitized subjects, the MAT was found to have superior discrimination performance compared with other testing modalities, including component-resolved diagnostics and basophil activation tests. Using functional principle component analysis, we identified 5 clusters or patterns of reactivity in the resulting dose-response curves, which at preliminary analysis corresponded to the reaction phenotypes seen at challenge.ConclusionThe MAT is a robust tool that can confer superior diagnostic performance compared with existing allergy diagnostics and might be useful to explore differences in effector cell function between basophils and MCs during allergic reactions.

Broad IgG repertoire in patients with chronic rhinosinusitis with nasal polyps regulates proinflammatory IgE responses

“…Mast cells infiltrate nasal polyp tissue more than basophils, and it has also been shown in a separate study that mast cell activation is a sensitive alternative assay to the Basophil Activation Test. 23 However, assessing FcεRI-mediated responses in basophils rather than mast cells is a well-established method, with various reports validating the reliability of this assay. 18,24,25 We had limited nasal polyp homogenates, which made it difficult to also assess mast cell activation and histamine release.…”

Recent developments and highlights in food allergy

“…BAT did not show a significant advantage. 76 In addition, promising results on the usage of passive sensitization strategies using the mast cell lines 77 or mast cell precursors 78 have been reported. Larger, real-life studies are demanded to confirm that passive sensitization strategies, which are technically more demanding but have the advantage of using serum instead of fresh blood, are as reliable as the conventional approach.…”

C‐reactive protein (CRP) rs3093059C predicts poor mizolastine response in chronic spontaneous urticaria patients with elevated serum CRP level

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